The involvement of nitric oxide (NO) in the reinforcing properties of opiate reward was studied by examining the effect of a NO precursor (L-arginine) and a NO synthase inhibitor (L-NAME) on the rate of intravenous self-administration of morphine. This experiment was investigated in male albino Sprague Dawley rats (300 ± 50 g). At doses of 5 and 10 mg/kg (i.p.), L-arginine decreased morphine self- administration significantly, while 20 and 60 mg/kg doses were not significantly effective. In addition, L-arginine per se induced self-administration behavior. At doses of 0.75, 1.25, 2.5, and 5 mg/kg (i.p.), L-NAME had no effect on self-administration, whereas injection of 5 mg/kg 60 minutes before the test did increase self-administration significantly. We may therefore conclude that NO is involved in the VTA-mesolimbic pathway, and it can be involved in the psychological dependence to morphine.